Universität zu Köln

Morris, Carolyn R., Habibovic, Aida, Dustin, Christopher M., Schiffers, Caspar, Lin, Miao-Chong, Ather, Jennifer L., Janssen-Heininger, Yvonne M. W., Poynter, Matthew E., Utermohlen, Olaf, Kroenke, Martin and van der Vliet, Albert (2022). Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease. Mucosal Immunol., 15 (5). S. 977 - 990. LONDON: SPRINGERNATURE. ISSN 1935-3456

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Abstract

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Morris, Carolyn R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Habibovic, Aida UNSPECIFIED UNSPECIFIED UNSPECIFIED Dustin, Christopher M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiffers, Caspar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Miao-Chong UNSPECIFIED UNSPECIFIED UNSPECIFIED Ather, Jennifer L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Janssen-Heininger, Yvonne M. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Poynter, Matthew E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermohlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Vliet, Albert UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-667727
DOI:	10.1038/s41385-022-00530-x
Journal or Publication Title:	Mucosal Immunol.
Volume:	15
Number:	5
Page Range:	S. 977 - 990
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1935-3456
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALTERNATIVELY ACTIVATED MACROPHAGES; ALVEOLAR MACROPHAGES; HYDROGEN-PEROXIDE; WOUND REPAIR; CELLS; AMPHIREGULIN; OXIDASES; NEURONS; MODEL; MICE Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66772